Senna is a known active ingredient for use as a laxative. Senna is an extract of the senna plant. The extract primarily comprises sennosides A+B. Sennosides A and B (sennosides, 5,5'-bis(.beta.-D-glucopyranosyloxy)-9,9', 10,10'-tetrahydric-4,4'-dihydroxy-10, 10'-dioxo 9,9'-bianthracene !-2,2'-dicarboxylic acid) are stereoisomeric bisanthrone glucosides. In addition, other sennosides (named sennosides C, D, E, etc.) have been identified which can have laxative action. Although these other sennosides are minor components, they are a part of natural senna extracts. The preferred source of Ca-sennosides is partially purified extracts from dried leaves of "Indian senna" (Cassia angustifolia) or "African senna" (Cassia acutifolia: Cassia senna), and commonly prepared as calcium salts. Other natural sources include extracts of rhubarb, aloe, aloin. However, these latter have a relatively low content of sennosides and are higher in contaminants. Standardized senna concentrates are another available form for sennosides, but would be less preferred as a source of sennosides. Standardized senna extracts are obtained from dried seed pods, and generally have a lower concentration of sennosides than available from semipurified calcium sennosides.
Calcium sennosides and standardized senna concentrates are commercially available. One source of commercially available calcium sennosides is Huhtamaki Leiras (Finland). The product is labeled as 60% Casennosides, contains 72.3% sennosides by analysis according to the U.S. Pharmacopia (Volume XXII, 1990, page 1246).
The sennosides themselves have little to no direct laxative activity. Rather, they are convened to the derived active moiety, rhein-9-anthrone, by colonic bacteria. Pharmacology studies demonstrate that rhein-9-anthrone has the greatest purgative action associated with use of sennosides. Senna extracts and sennosides are water soluble. Sennosides are poorly absorbed from the small intestine, but the hydrolysis products generated in the colon (e.g., rhein or rhein-9-anthrone) are readily absorbed from both the small intestine and the colon.
Contact of the rhein with the mucosa produces increased propulsive peristaltic contractions of the colon which accelerate movement of contents through the colon. Since rhein acts upon contact with lumenal mucosa of the large intestine, its laxative effect is dependent upon generation of sufficient levels of the drug in the lumen of the colon.
Commercially available laxative whose active ingredient is senna, or sennosides, are in dose forms which deliver senna to the stomach or to the small intestine. At doses which produce maximal laxation, the sennosides also evoke secondary episodes of diarrhea.
Applicant has surprisingly discovered that delivery of sennosides to the colon as a rapidly dissolving matrix, or in a solubilized form, produces maximal laxation at doses lower than those found in commercial laxatives. Applicant has also surprisingly discovered that sennosides delivered to the colon are effective at doses which result in diminished secondary episodes of diarrhea relative to duodenally delivered senna.